Receptors for the Fc region of antibodies (FcR) play a coordinating role in immunity. They are expressed on various types of cells and mediate functions ranging from endocytosis, phagocytosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and cytokine production, to facilitation of antigen presentation. Antigen presentation represents a process in which antigens are captured, targeted to appropriate compartments, and processed before binding to major histocompatibility complex (MHC) molecules.
Leukocyte FcR for IgG (FcγR) comprises a multigene family, divided into three classes (FcγRI, II, and III) based on differences in receptor structure, cell distribution, and affinity for IgG (Van de Winkel, et al. (1993) Immunol. Today 14:215). FcγR molecules can potently enhance antigen presentation. The type of FcγR involved has been shown to be a crucial determinant for the types of epitopes presented by the antigen-presenting cell (Amigorena, et al. (1998) J. Exp. Med. 187:505).
The human high-affinity receptor for IgG, hFcγRI (CD64), is constitutively expressed on antigen-presenting cells such as monocytes, macrophages, and dendritic cells. CD64 is a preferred trigger receptor for use in therapy because it is (1) expressed primarily on immune effector cells; (2) mediates cytotoxic activities (e.g., ADCC, phagocytosis); and (3) mediates enhanced antigen presentation of antigens targeted to them. In fact, human CD64-targeted antigens are presented efficiently both in vitro and in vivo (Liu, et al. (1996) J. Clin. Invest. 98:2001; Heijnen, et al. (1996) J. Clin. Invest. 97:331). Accordingly CD64 is a therapeutically important receptor for mediating immune functions.